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Establishment of Gastric Cancer Patient-derived Xenograft Models and Primary Cell Lines
Published on: July 19, 2019
Establishment and characterization of multidrug-resistant gastric cancer cell lines
Xiaotian Zhang1, Masakazu Yashiro, Hong Qiu
1Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Aim:
The aim of this study was to establish drug-resistant cell lines and to elucidate mechanisms leading to multi-drug resistance in gastric cancer.
Materials And Methods:
Five cancer cell lines resistant to 5-fluorouracil, paclitaxel, oxaliplatin, irinotecan, or gemcitabine, were respectively established from a parent gastric cancer cell line, OCUM-2M, by stepwise exposure to each chemotherapeutical agent.
Results:
Cell death by apoptosis induced by anti-cancer drugs was low in 5 chemo-resistant cell lines. Percentage of cells in S and G(0)/G(1) phase was low in cell lines resistant to oxaliplatin or irinotecan. Cell lines resistant to paclitaxel, oxaliplatin, and gemcitabine showed multi-drug resistance. Alterations in MRP, DAPK1, or DAPK2 expression were found in multi-drug resistant cell lines.
Conclusion:
The cell-cycle distribution and alterations of MRP, DAPK1, and DAPK2 genes may be integral part of mechanisms responsible for chemo-resistance. These cell lines might be useful to study molecular mechanisms leading to multi-drug resistance.
Insights
Researchers developed drug-resistant gastric cancer cell lines to study multi-drug resistance mechanisms. Findings suggest cell-cycle changes and gene alterations in MRP, DAPK1, and DAPK2 are key to chemo-resistance.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Gastric cancer remains a significant global health challenge.
- Acquired chemo-resistance is a major obstacle in effective gastric cancer treatment.
- Understanding resistance mechanisms is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To establish multi-drug resistant gastric cancer cell lines.
- To investigate the molecular mechanisms underlying chemo-resistance.
- To provide valuable tools for studying drug resistance in gastric cancer.
Main Methods:
- Established five distinct gastric cancer cell lines (OCUM-2M) resistant to specific chemotherapeutic agents (5-fluorouracil, paclitaxel, oxaliplatin, irinotecan, gemcitabine) through stepwise drug exposure.
- Assessed apoptosis induction by anti-cancer drugs.
- Analyzed cell-cycle distribution (S and G(0)/G(1) phases).
- Examined gene expression alterations in Multidrug Resistance Protein (MRP), DAPK1, and DAPK2.
Main Results:
- Established five chemo-resistant gastric cancer cell lines.
- Observed reduced apoptosis induction by anti-cancer drugs in resistant cell lines.
- Identified altered cell-cycle distribution in oxaliplatin- and irinotecan-resistant lines.
- Found multi-drug resistance in paclitaxel-, oxaliplatin-, and gemcitabine-resistant lines.
- Detected alterations in MRP, DAPK1, and DAPK2 gene expression in multi-drug resistant lines.
Conclusions:
- Cell-cycle distribution and alterations in MRP, DAPK1, and DAPK2 gene expression are implicated in chemo-resistance mechanisms.
- The developed cell lines serve as a valuable resource for further research into gastric cancer multi-drug resistance.
- These findings contribute to a deeper understanding of the molecular basis of therapeutic failure in gastric cancer.
